What exactly is the Technosphere® Platform?

One of the largest organs in your body are the lungs. Picture the size of a full tennis court and that is roughly the surface area of both lungs in a typical adult. Running through those lungs are airways whose total length measures 1,500 miles – that’s the distance between Chicago and Las Vegas, New York to Albuquerque, and Los Angeles to Nashville.

Simply put, the lungs create a wonderful platform for effective drug delivery. MannKind’s Technosphere technology recognizes this and provides the distinct advantage of rapid, deep lung drug delivery. The effect is similar to intravenous delivery (I.V.; within a vein) and has the added benefit of bypassing the liver which can be especially helpful in reducing systemic side effects.

Examining it closer, it helps to look at inhalation, air flow travel, and the exhale. When you breathe in, air is drawn into the lung and flows down curving, narrowing airways that end in the air sacs or alveoli. When air is exhaled, the flow is reversed. Between the end of an inhalation and the start of exhalation, the air in the lung is stationary. To reach the deep lung, inhaled particles must be carried by the air stream and have enough momentum to continue through the stationary air to collide with the lung surface.

Particles that can reach the lung have aerodynamic diameters between 0.5 µm and 5-6 µm (1 µm is 1 micro-meter or about 0.00004 inches). Particles that are larger than 6 µm will leave the air stream and hit the back of your mouth and throat; smaller than 0.5 µm wouldn’t have the ability to reach the lungs and would simply get exhaled.

“The average Technosphere particle is about 2-2.5 µm which is in the middle of the respirable range,” explains Marshall Grant, PhD, MSc, Executive Director, Clinical Pharmacology & Research for MannKind Corporation. “The particle size distribution is a major reason Technosphere powders are highly efficient in delivering drug to the lungs than other dry powder inhalers (DPIs).”

The Technosphere particles in FDA-approved Afrezza® (insulin human) Inhalation Powder and Tyvaso DPI™ (treprostinil) Inhalation Powder are manufactured by different processes and possess different characteristics. But both are made up of small crystals of FDKP (fumaryl diketopiperazine), MannKind’s proprietary molecule. FDKP provides high solubility and fast dissolution at physiologic pH – and more importantly – can crystallize and form particles in the range appropriate for optimum delivery to the lungs.

When Technosphere powder reaches the lung surface, the FDKP and drug dissolve. The FDKP is then rapidly cleared from the lung into systemic circulation. The FDKP is not metabolized, but rather excreted primarily in the urine. Another value of Technosphere powders has been their versatility – they are compatible with a wide range of doses with different types of drugs.

MannKind’s Technosphere powders are delivered into the lung’s airstream via an inhalation device or DPI (dry powder inhaler). The breath-powered inhalers (Dreamboat® being the most common version) provide excellent delivery efficiency and are proven to deliver up to 70% of the dry-powder dose deep into the lungs. Our DPI are designed to be simple, easy to use and discreet. For patients, imagine having a drug in the convenient form of an inhaler that fits in the palm of your hand. This approach allows patients to not only take control of their health but do it while going about their day and enjoying life more humann.

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NTM Lung Disease on the Rise

“I cough every morning upon waking, so I don’t feel rested.” “Imagine not being able to breathe.” “Anxiety ruins everything about you – it’s not a normal life.” “You just exist from day to day and week to week.” These are a sampling of comments about the most bothersome symptoms from living with Nontuberculous Mycobacteria (NTM) shared in a study from NTM Info & Research, Inc. The statements are unfortunately typical and those with NTM often have unpredictable day-to-day health functioning and reduced quality of life.

NTM lung disease is a serious infection that is caused by bacteria that are common in the environment and can cause lung damage. The reality is that we are all exposed to these bacteria in our day-to-day lives – more than 120 species of mycobacteria have been identified. These common bacteria exist in water and soil particles that are in the air, wet places like hot tubs, steamy bathrooms, dishwashers, and even the dewy ground we walk on at the park. But not everyone is at risk of getting NTM lung disease just because they are exposed.

Those predisposed often have underlying conditions such as asthma, COPD, and bronchiectasis, which makes them prone to NTM infection. NTM is not considered to be contagious. Women over the age of 65 make up the majority of those impacted, with a predominance in those of Caucasian and Asian descent.

A rare disease, NTM can often be difficult to diagnose. Many will experience coughing, fatigue, weight loss and shortness of breath – all of which are common with other lung disease symptoms and other conditions like tuberculosis. With NTM, symptoms often worsen, and that is a marker not to be ignored.

It is estimated that some 86,000 individuals are living with NTM lung diseases, and it is on the rise growing 8% each year. Coastal regions including Gulf States have higher rates of infection accounting for 70% of annual NTM cases.

While no cure is available, treatments to manage NTM are available. Treatment for NTM involves antibiotic and multidrug regimens with duration lasting from months to years with tolerability and adverse reactions to treatment which often leads to a lack of adherence to therapy.

There is a valuable need to develop medicines that are well tolerated and effective that lends to consistent patient use and alleviates symptoms of NTM lung disease. MannKind continues to progress MNKD-101 (Clofazimine) for the treatment of NTM.

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Release Details

Studies Show Early Promise of MannKind's Cancer Immunotherapy Program in Melanoma, Prostate Cancer and Other Solid Malignancies

10/29/09
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Studies Show Early Promise of MannKind's Cancer Immunotherapy Program in Melanoma, Prostate Cancer and Other Solid Malignancies

WASHINGTON--(BUSINESS WIRE)--Oct. 29, 2009-- Results of two phase 1 studies demonstrate that the novel, investigational cancer vaccines MKC1106-MT and MKC1106-PP are well-tolerated and show encouraging immune response rates and objective tumor response in advanced melanoma, prostate cancer and other solid malignancies, setting the stage for phase 2 studies. The data are being presented at the International Society for Biological Therapy of Cancer 2009 Annual Meeting.

MKC1106-MT is an active immunotherapeutic product consisting of three components, a DNA plasmid and two synthetic peptides, each of which is administered separately by the unique route of intranodal injection and together are designed to target two tumor-specific antigens that are commonly expressed by melanoma tumor cells. MKC1106-PP is a similar agent that is designed to target two specific tumor antigens commonly expressed by various solid tumor cells.

“MKC1106-MT and MKC1106-PP met the primary end-points of both trials and, in addition, showed early evidence of clinical benefit, which marks an important step forward for MannKind’s oncology portfolio,” said Peter Richardson, MRCP, Corporate Vice President and Chief Scientific Officer, MannKind Corporation. “These encouraging results set the stage to move into phase 2 trials with these innovative, targeted therapies, which represent the cornerstone of our cancer immunotherapy program.”

MKC-1106 MT Study Design and Key Findings

In an ongoing, open-label, multicenter trial, 18 patients with advanced melanoma were treated with MKC1106-MT and were evaluated after each therapeutic cycle of six weeks. Patients demonstrating a clinical response or no evidence of disease progression remained in the clinical trial and received up to eight cycles of treatment over one year. In all patients, repeat administration of the treatment was well tolerated with limited adverse events.

Findings reveal an immune response rate of greater than 40 percent, defined as the percentage of patients who showed elevated numbers of antigen specific T cells in the blood upon immunization, and preliminary evidence of clinical benefit. Of the 18 patients treated, 14 had visceral metastases and the remaining four had metastases confined to the lymphatic system. All four patients with lymphatic metastatic disease achieved durable objective responses (partial response based on tumor imaging [RECIST criteria]), an unexpected outcome for a phase 1 study in this type of setting. A subset analysis identified the presence of melanoma-specific T cells at baseline in the patients with lymphatic metastatic disease. Overall, these results identified patients that could benefit most from this type of therapy and will be used to design the phase 2 trial of MKC1106-MT in advanced melanoma.

“Cancer vaccines have been explored in the past with very limited success to curb the disease progression of malignant melanoma,” said Antoni Ribas, MD, Associate Professor, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA. “The promising preliminary results of this ongoing study warrant further evaluation of MKC1106-MT in advanced disease and as an adjuvant therapy.”

MKC1106-PP Study Design and Key Findings

In the second study, 26 patients with advanced cancer who had diverse tumor types, metastatic disease and/or progressive, refractory disease were treated with MKC1106-PP. Patients were evaluated after two therapeutic cycles (12 weeks) and again at 24 weeks, as applicable. Patients demonstrating a clinical response or no evidence of disease progression remained in the clinical trial and received up to six cycles of treatment over nine months. In all patients, repeat administration of the treatment was well tolerated with limited adverse events.

As with the MKC1106-MT trial, an immune response rate and encouraging preliminary evidence of clinical benefit were achieved. In this study, an immune response rate of 60 percent was observed. Of the 26 patients treated, seven patients achieved clinical responses defined as partial response (RECIST), change in PSA doubling time or stable disease for at least six months. Patients attaining an immune response against both antigens, persisting throughout the first two cycles of therapy, were more likely to show clinical benefit, setting the stage for further evaluation in phase 2 studies.

“These findings lay the foundation for additional trials evaluating the clinical benefit of MKC1106-PP in select indications,” said Nicholas J. Vogelzang MD, Chair and Medical Director, Developmental Therapeutics and Co-Chair, GU Committee, US Oncology Research, Comprehensive Cancer Centers of Nevada. “Further study of this investigational agent’s mechanism of action will also be important in assessing its promise in biomarker-defined patient populations.”

About MannKind Corporation

MannKind Corporation (Nasdaq: MNKD) focuses on the discovery, development and commercialization of therapeutic products for patients with diseases such as diabetes and cancer. Its pipeline includes AFRESA®, MKC253, MKC1106-PP, and MKC1106-MT. MannKind has submitted an NDA to the FDA requesting approval of AFRESA for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia. Its other programs are currently in Phase 1 clinical trials. MannKind maintains a website at http://www.mannkindcorp.com to which MannKind regularly posts copies of its press releases as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to e-mail alerts that are sent automatically when MannKind issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the website.

Source: MannKind Corporation

MannKind Corporation
Peter Richardson
Chief Scientific Officer
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MannKind Corporation
Matthew J. Pfeffer
Chief Financial Officer
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